ABSTRACT One in nine individuals older than age 65 has Alzheimer?s disease (AD). Globally the annual cost of AD and other dementias is estimated to exceed $600 billion. The asymptomatic phase of AD can last up to 20 years, and the most effective treatment would be administered during this period. To effectively address AD, there is a critical need to identify biomarkers and risk factors associated with the earliest stages of AD. The goals of this proposal are to systematically evaluate cognitive function in a normative elderly population and assess its association with retinal thickness and social and economic stress, and to quantify how vascular risk factors moderate these associations. The central hypothesis is that both retinal thickness and stress predict cognitive function, but that these associations are moderated by BMI, hypertension, smoking, and gender. This study will assess 100 men and women (65+ years) that are a subset of a study initiated in 1989. We will test our hypothesis with the following three specific aims: Aim 1: To test the hypothesis that reduced retinal thickness predicts decreased cognitive function in a normative aging population. A 60-minute battery of 10 clinical neuropsychological instruments will be used to characterize cognition across the major cognitive domains that probe multiple brain regions. A standard set of retinal nerve fiber layer thickness measurements will also be taken for each participant at a local eye clinic, and tested for their ability to predict a series of individual cognitive tests. Aim 2: To test the hypothesis that increased economic and social stress predicts decreased cognitive function in a normative aging population. Our standard comprehensive survey consisting of economic and social stress indicators will again be measured for each participant. The survey includes measures of economic circumstances, emotional distress, and strengths or difficulties in close relationships. These economic and social stress measures will be tested for their ability to predict each set of individual cognitive tests. Aim 3. To test the hypothesis that vascular risk factors and gender moderate the associations among cognitive function and retinal nerve fiber layer thickness (Aim 1) and economic and social stress (Aim 2). We will test whether current BMI (normal weight vs. overweight/obese), hypertension, smoking, and gender moderate the association between retinal thickness, economic pressure, social stress and cognitive functioning. The outcome of the proposed work will be an understanding of the association between retinal thickness, economic and social stress, and the spectrum of cognitive function in an elderly population and how these associations may be moderated by gender and vascular risk factors. This research has broad public health significance as it tests the effectiveness of assessments that would be appropriate to screen thousands of individuals at minimal cost towards the identification of those most at risk of developing AD, and who would benefit most from early-stage interventions as they become available.